An ultra-thin thrombectomy wire will be developed that uses transverse ultrasound waves at its tip to selectively and safely disintegrate intracranial blood clot without damage to the adjacent structures. The proposed system challenges the paradigm of current available therapies which rely on either relatively slow pharmacologic action or en block removal of clot. The goal is to provide rapid and immediate perfusion of ischemic tissue as the cornerstone of effective treatment for acute ischemic stroke. There are currently only two FDA-approved therapies: (1) Pharmacologic clot dissolution with tissue plasminogen activator (tPA); and (2) Mechanical thrombectomy with a basket-type mechanical device, the Merci retriever. tPA increases the risk of intracranial hemorrhage, and must be started within 3 hours of onset of the ischemic event thus limiting its use to less than 5% of current stroke victims. The Merci device, which is employed outside of the tPA treatment window, is marginally effective with less than half of the cases being recanalized. The Merci retriever is known to let soft clot escape and may require multiple passes that increase procedure time and risk. Traditionally mechanical thrombectomy devices either rely on removal of clot in toto or mechanical disintegration with subsequent aspiration, requiring devices that are larger than desirable in the cerebral vasculature. To overcome these limitations we propose to develop a low-profile and atraumatic thrombectomy device that uses tailored transmission of ultrasonic energy around an ultra-thin wire that can be advanced through standard neuroangiographic microcatheters. Recanalization is anticipated within seconds or minutes expanding the window of treatment opportunity that so far had to take into account the 2-hours average time tPA infusion requires for flow restoration. The proposed system has the potential to increase the number of patients treatable 5-fold, benefiting annually at 200,000 patients in the United States alone. This essentially changes the paradigm of stroke from a rehabilitation orientation to treatment focus. The objective of this research is to refine the design of a prototype system to demonstrate efficacy and safety. We propose three interrelated specific aims: Stroke carries a severe toll in terms of loss of life and disability for patients and their families. Stroke is the third cause of death in the United States and the leading cause of disability in terms of cost of care and loss of productivity. According to the newest data from the American Stroke Association, each year approximately 700,000 individuals experience a new or recurrent stroke and 160,000 of these events are fatal. This project seeks to find a new treatment to give stroke victims an option other than rehabilitation. [unreadable] [unreadable] [unreadable]